Systems Neuroscience: From Networks to Behaviour. (360G-Wellcome-096973_Z_11_Z)

Our overarching aim is to understand·the·. spatial and temporal patterns of activity during neocortical seizures. Ultimately, we want to understand what happens at the edge of seizure, at the boundary between core recruited territories, and surrounding areas where firing is suppressed by an inhibitory restraint (penumbral territory). This boundary may or may not be fixed; in some instances, the penumbral territory is subsequently recruited, in which case the boundary shifts, but in other instances, further recruitment is prevented, and the boundary remains fixed. A key goal therefore is to understand these two possible outcomes, namely the recruitment of new territories or the failure to spread. · Prior work has indicated that the boundary may be set by an inhibitory restraint of the penurhbral territory. We will study epileptic activity patterns in several relevant transgenic mouse lines, and also in vivo and in vitro human recordings. Various studies have shown that raised intraneuronal Cl levels are found in epileptic tissue. Low intraneuronal Cl is required for functional GABAergic inhibition, and so raised intraneuronal Cl may lead to a disinhibited network. We will investigate the role of Cl dysregulation in the failure of the restraint.